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A robust preparation method for the amyloidogenic and intrinsically disordered amyloid-α peptide.

ABSTRACT: Recent findings suggest that amyloid-β (Aβ) may not be the only peptidic culprit for the cognitive decline observed in patients with Alzheimer's disease. A C-terminal fragment of Aβ, amyloid-α (Aα), also known as p3, has been shown to form amyloidogenic oligomers and fibrils more rapidly than Aβ. However, the insolubility and aggregation propensity of this 24-26-residue peptide make it exceptionally difficult to produce, purify, and subsequently study. This paper reports a reproducible, multi-step method for the purification and pre-treatment of Aα and related analogues, yielding 95%-99% pure peptides. We anticipate that the methods described herein will permit previously inaccessible biophysical and biological experiments that may be critical to understanding the role of this too long overlooked peptide in AD disease pathology.

SUBMITTER: Kuhn AJ

PROVIDER: S-EPMC9452447 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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A robust preparation method for the amyloidogenic and intrinsically disordered amyloid-α peptide.

Kuhn Ariel J AJ Raskatov Jevgenij A JA

Journal of peptide science : an official publication of the European Peptide Society 20220506 10

Recent findings suggest that amyloid-β (Aβ) may not be the only peptidic culprit for the cognitive decline observed in patients with Alzheimer's disease. A C-terminal fragment of Aβ, amyloid-α (Aα), also known as p3, has been shown to form amyloidogenic oligomers and fibrils more rapidly than Aβ. However, the insolubility and aggregation propensity of this 24-26-residue peptide make it exceptionally difficult to produce, purify, and subsequently study. This paper reports a reproducible, multi-st ...[more]

PMID: 35484922

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